Congenital cytomegalovirus (CMV) infection is an important cause of mental retardation in this country. One to 2% of all newborns are infected with CMV, and approximately 10% of these children manifested significant neurologic impairment. We propose to investigate relationships between maternal and fetal CMV infection, utilizing a guinea pig model. We will focus on the relationship between timing of maternal infection, maternal immune status, and subsequent fetal involvement. Sixty animals, approximately half seronegative, will be infected at various times in pregnancy. A portion of the pregnancies will be allowed to go to term, while others will be interrupted at various stages of gestation. Mothers and their fetuses will be sacrificed, and viral cultures obtained on a variety of organs including maternal salivary gland, lung, spleen, liver, kidney, and placenta, fetal brain, lung, spleen, liver and kidney. In some animals, quantitative assessment of the amount of virus present in various organs will be determined by use of plaquing techniques. Serologic studies will be performed on mothers and fetuses. All virus-positive specimens will be examined histologically. The effectiveness of a tissue-passaged live CMV vaccine in protecting mothers against later challenge with varying doses of virus will be assessed by immunizing a group of animals prior to conception and subsequently performing studies similar to those done in the non-immunized animals. Data obtained will enhance our understanding of human CMV infection in pregnancy, and provide background information pertinent to future use of CMV vaccines.